L-O-(2-malonyl)tyrosine (L-OMT) a new phosphotyrosyl mimic suitably protected for solidphase synthesis of signal transduction inhibitory peptides

Article abstract of DOI:10.1016/0040-4039(95)00890-O

A new phosphotyrosyl (pTyr) mimic L-O-(2-malonyl)tyrosine (L-OMT, 4) utilizes a malonyl structure in place of the parent phosphate group. This compound is stable to protein-tyrosine phosphatases and has advantages over phosphonate-based pTyr mimics in that protection of the malonyl group as its diester allows passage of the OMT across cell membranes, with subsequent esterase-mediated liberation of the free diacid once inside cells. Herein is reported the synthesis of N^α-Fmoc-L-OMT-O,O-(ferf-butyl)₂ (5) for the solid-phase synthesis of L-OMT containing peptides as modulators of cellular signal transduction. Additionally included is the preparation of N^α-Fmoc-L-OMT-O,O-(n-butyl)₂ (6) for the direct solid-phase synthesis of OMT-peptide diester prodrugs for use in cell-based studies.